Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1833

Hefti, H P; Frese, M; Landis, H; Di Paolo, C; Aguzzi, A; Haller, O; Pavlovic, J (1999). Human MxA protein protects mice lacking a functional alpha/beta interferon system against La crosse virus and other lethal viral infections. Journal of Virology, 73(8):6984-6991.

[img]
Preview
PDF
972kB

Abstract

The human MxA protein is part of the antiviral state induced by alpha/beta interferon (IFN-alpha/beta). MxA inhibits the multiplication of several RNA viruses in cell culture. However, its antiviral potential in vivo has not yet been fully explored. We have generated MxA-transgenic mice that lack a functional IFN system by crossing MxA-transgenic mice constitutively expressing MxA with genetically targeted (knockout) mice lacking the beta subunit of the IFN-alpha/beta receptor (IFNAR-1(-/-) mice). These mice are an ideal animal model to investigate the unique antiviral activity of human MxA in vivo, because they are unable to express other IFN-induced proteins. Here, we show that MxA confers resistance to Thogoto virus, La Crosse virus, and Semliki Forest virus. No Thogoto virus progeny was detectable in MxA-transgenic mice, indicating an efficient block of virus replication at the primary site of infection. In the case of La Crosse virus, MxA restricted invasion of the central nervous system. In contrast, Semliki Forest virus multiplication in the brain was detectable in both MxA-expressing and nonexpressing IFNAR-1(-/-) mice. However, viral titers were clearly reduced in MxA-transgenic mice. Our results demonstrate that MxA does not need the help of other IFN-induced proteins for activity but is a powerful antiviral agent on its own. Moreover, the results suggest that MxA may protect humans from potential fatal infections by La Crosse virus and other viral pathogens.

Citations

98 citations in Web of Science®
99 citations in Scopus®
Google Scholar™

Downloads

152 downloads since deposited on 11 Feb 2008
97 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:1 August 1999
Deposited On:11 Feb 2008 12:25
Last Modified:27 Nov 2013 17:03
Publisher:American Society for Microbiology
ISSN:0022-538X
Related URLs:http://jvi.asm.org/cgi/content/abstract/73/8/6984
PubMed ID:10400797

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page